This paper provides the results of a study evaluating the efficacy and safety of etiotropic therapy in patients hospitalized with SARS-CoV-2 infection. Objective. Тo evaluate the efficacy and safety of favipiravir (Areplivir) in patients with coronavirus disease 2019 (COVID-19) and compare it with recommended standard therapy. Patients and methods. Two hundred men and women aged between 18 and 80 years with COVID-19 were randomized into this study. The experimental group included patients who received favipiravir, whereas the control group comprised patients who received causal therapy in accordance with the latest version of the temporary methodical recommendations of the Ministry of Health of Russia ‘Prevention, diagnosis, and treatment of coronavirus infection (COVID-19).’ The efficacy and safety of therapy were evaluated by assessing clinical improvement using the WHO Ordinal Scale for Clinical Improvement, clinical and laboratory parameters, findings of chest computed tomography (CT), and elimination of SARS-CoV-2. We also analyzed the frequency and type of adverse events, need for invasive and non-invasive ventilation, and death rates. Results. Our analysis has demonstrated significant benefits of favipiravir over standard therapy in terms of the time to clinical improvement (in the experimental group it was 4 days shorter on average), time to recovery, frequency of recovery after 10 days (44% of patients from the experimental group and 10% of patients from the control group had no clinical signs of the disease at this time-point), and frequency of virus elimination by day 10 of therapy. Treatment with favipiravir was associated with a significant improvement in the lung condition (according to CT), normalization of laboratory parameters, and saturation level. Favipiravir has demonstrated a good safety profile similar to that of standard therapy. There was no difference in the frequency of adverse events between the experimental and control groups. Conclusion. The use of favipiravir for the treatment of SARS-CoV-2 infection reduced the time to clinical improvement by 4 days on average compared to standard therapy, ensured improvement of the lung condition (according to CT scans), and facilitated virus elimination in more than 90% of patients, thereby promoting faster recovery. Favipiravir had a good safety profile and was well tolerated by patients. This treatment regimen was shown to be effective, sufficient, and clinically reasonable to achieve good outcomes. Timely initiation of therapy with favipiravir (Areplivir) improves disease prognosis and reduces the global socioeconomic burden of the current pandemic. Key words: COVID-19, Areplivir, coronavirus, causal therapy, favipiravir

Aim: The present paper aims to systematize data concerning the prevalence and risk of dental erosion (DE) in adult patients with gastroesophageal reflux disease (GERD) compared to controls. Materials and methods: Core electronic databases, i.e., MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, and the Russian Science Citation Index (RSCI), were searched for studies assessing the prevalence and risk of DE in adult GERD patients with publication dates ranging from 1 January 1985 to 20 January 2022. Publications with detailed descriptive statistics (the total sample size of patients with GERD, the total sample size of controls (if available), the number of patients with DE in the sample of GERD patients, the number of patients with DE in the controls (if available)) were selected for the final analysis. Results: The final analysis included 28 studies involving 4379 people (2309 GERD patients and 2070 control subjects). The pooled prevalence of DE was 51.524% (95 CI: 39.742–63.221) in GERD patients and 21.351% (95 CI: 9.234–36.807) in controls. An association was found between the presence of DE and GERD using the random-effects model (OR 5.000, 95% CI: 2.995–8.345; I2 = 79.78%) compared with controls. When analyzing studies that only used validated instrumental methods for diagnosing GERD, alongside validated DE criteria (studies that did not specify the methodologies used were excluded), a significant association between the presence of DE and GERD was revealed (OR 5.586, 95% CI: 2.311–13.503; I2 = 85.14%). Conclusion: The meta-analysis demonstrated that DE is quite often associated with GERD and is observed in about half of patients with this extremely common disease of the upper gastrointestinal tract.

Introduction. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus (severe acute respiratory syndrome-related coronavirus 2). COVID-19 is now expected to stay with us for many years as a recurring disease. Molnupiravir and favipiravir are oral antiviral drugs with anti-RNA polymerase activity. The Russian Health Ministry has approved molnupiravir and favipiravir for the treatment of COVID-19. The study describes development and validation of high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of β-D-N4-Hydroxycytidine and favipiravir in human blood plasma. The method could be applied in pharmacokinetic study of molnupiravir and favipiravir.Aim. The aim of this study is to develop and validate a HPLC-MS/MS bioanalytical method for the determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma.Materials and methods. The determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma by HPLC-MS/MS. The samples were processed by 0.1 % formic acid in acetonitrile. Internal standard: promethazine. Mobile phase: 0.01 mol/L Ammonium formate buffer solution (Eluent A), 0.1 % formic acid and 0.08 % aqueous ammonia in water/acetonitrile 10 : 90 (Eluent B). Column: Shim-pack GWS C18, 150 × 4.6 mm, 5 μm. Analytical range: 50.00–10000.00 ng/mL for β-D-N4-Hydroxycytidine, 250.00–20000.00 ng/mL for favipiravir in human plasma. Ionization source: electrospray ionization. Detection conditions: 260.00 m/z → 82.10 m/z, 260.00 m/z → 111.00 m/z, 260.00 m/z → 127.95 m/z (β-D-N4-Hydroxycytidine); 156.15 m/z → 65.95 m/z, 156.15 m/z → 85.00 m/z, 156.15 m/z → 113.10 m/z (favipiravir); 285.05 m/z → 198.05 m/z (promethazine).Results and discussion. This method was validated by selectivity, suitability of reference standard, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability.Conclusion. The HPLC-MS/MS method for quantitative determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma was developed and validated. The analytical range was 50.00–10000.00 ng/mL for β-D-N4-Hydroxycytidine, 250.00–20000.00 ng/mL for favipiravir in human plasma. This method was applied to investigate the pharmacokinetics of molnupiravir and favipiravir.

Цель исследования-изучить эффективность и безопасность применения препарата фавипиравир (Арепливир) у больных COVID-19 по сравнению с рекомендованной стандартной терапией. Материал и методы. В исследование были рандомизированы 200 мужчин и женщин в возрасте от 18 до 80 лет с COVID-19. Основную группу составили пациенты, получавшие лечение препаратом фавипиравир, в группе сравнения пациентам назначали этиотропную терапию в соответствии с актуальной версией Временных методических рекомендаций Минздрава России по профилактике, диагностике и лечению новой коронавирусной инфекции (COVID-19). Эффективность и безопасность терапии определяли на основании оценки клинического улучшения по Категориальной шкале клинического улучшения Всемирной организации здравоохранения, клинико-лабораторных данных, результатов компьютерной томогра

The article presents the data from an open, two-stage, multicenter study on the efficacy and safety evaluation of a combined drug (a fixed combination of nirmatrelvir 300 mg and ritonavir 100 mg) in the complex therapy in COVID-19 patients.The aim of the study was to assess the safety, tolerability and pharmacokinetic parameters of the fixed combination of nirmatrelvir 300 mg and ritonavir 100 mg in healthy volunteers, the efficacy and safety assessment of the drug in the combination therapy compared with the standard therapy in COVID-19 patients.Material and methods. An open two-stage multicenter clinical study to assess the main pharmacokinetic parameters, safety, and efficacy against COVID-19 of the drug nirmatrelvir 300 mg and ritonavir 100 mg combination (Skyvira® PROMOMED RUS LLC, Russia) in the adult population, included 2 stages. At stage 1, safety, tolerability and pharmacokinetic parameters were evaluated in healthy volunteers (over 18 years of age) in order to confirm their comparability with the literature data known for a set of active substances. Phase 2 assessed efficacy and safety in COVID-19 patients. As a part of the second stage, the study involved 264 patients (men and women aged 18 to 80 years), who had been divided into two groups. The first group patients (n=132) received the study drugs (nirmatrelvir 300 mg and ritonavir 100 mg) – 1 tablet twice a day with an interval of 12±2 hours for 5 days in combination with pathogenetic and symptomatic therapy. The second group patients (n=132) received standard therapy in accordance with the approved Temporary Guidelines for the Prevention and Treatment of Novel Coronavirus Infection (Version 15 dated February 22, 2022).Results. During the study, none of the patients from the (nirmatrelvir + ritonavir) group experienced a transition of the COVID-19 course to a heavier severity level, in contrast to the patients in the standard therapy group. The study participants included patients with comorbidities (68% of the general population), with risk factors for COVID-19 progression to a heavier severity level and the risk of hospitalization (75% of the general population). There were no cases of COVID-19 progression to a heavier severity level in the study drug group. By the 6th day, in the nirmatrelvir + ritonavir group, the proportion of the patients who had achieved a complete recovery was twice more and amounted to 35.61% (p=0.0001), and the proportion of the patients with a negative RNA analysis to SARS-CoV-2 was 20% higher than in the comparison group, and amounted to 82.58% (p=0.0001). The fixed nirmatrelvir + ritonavir combination therapy has a favorable safety profile comparable to the standard therapy. The identified adverse reactions were transient in nature and did not require discontinuation of therapy or changes in the treatment regimen.Conclusion. The fixed nirmatrelvir + ritonavir combination has a favorable safety profile in COVID-19 patients, comparable to the standard therapy. The data obtained demonstrate a clinical and pharmacoeconomic feasibility of including the fixed (nirmatrelvir + ritonavir) combination in the COVID-19 treatment regimen.